Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine
Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepati...
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| Veröffentlicht in: | PloS one 2008-08, Vol.3 (8), p.e2954-e2954 |
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| creator | Makidon, Paul E Bielinska, Anna U Nigavekar, Shraddha S Janczak, Katarzyna W Knowlton, Jessica Scott, Alison J Mank, Nicholas Cao, Zhengyi Rathinavelu, Sivaprakash Beer, Michael R Wilkinson, J Erby Blanco, Luz P Landers, Jeffrey J Baker, Jr, James R |
| description | Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.
Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.
Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy. |
| doi_str_mv | 10.1371/journal.pone.0002954 |
| format | Article |
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Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.
Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0002954</identifier><identifier>PMID: 18698426</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adjuvants, Immunologic ; Alum ; Aluminum ; Aluminum sulfate ; Animal models ; Animals ; Antibodies ; Antibody Formation ; Antigens ; Aqueous solutions ; Bell's palsy ; Bells palsy ; Biochemistry/Drug Discovery ; Biochemistry/Protein Chemistry ; Cell-mediated immunity ; Chemistry, Pharmaceutical ; Chronic infection ; Cold storage ; Control stability ; Cytomegalovirus ; Developing countries ; Dosage Forms ; Electrostatic properties ; Emulsions ; Enzymes ; Evaluation ; Global health ; Guinea pigs ; Health aspects ; Hepatitis ; Hepatitis B ; Hepatitis B surface antigen ; Hepatitis B Surface Antigens - administration & dosage ; Hepatitis B Surface Antigens - immunology ; Hepatitis B vaccines ; Hepatitis B Vaccines - administration & dosage ; Hepatitis B virus ; High temperature ; Humans ; Hydration ; Hydrophobicity ; Immune response ; Immune system ; Immunity ; Immunization ; Immunoassay ; Immunogenicity ; Immunoglobulin A ; Immunoglobulin G ; Immunoglobulin G - blood ; Immunoglobulins ; Immunology/Antigen Processing and Recognition ; Immunology/Immune Response ; Immunology/Innate Immunity ; Infection ; Infectious Diseases/Epidemiology and Control of Infectious Diseases ; Infectious Diseases/Viral Infections ; Influenza ; Interferon ; Laboratory animals ; Lymphocytes B ; Lymphocytes T ; Medicine ; Mice ; Mucosa ; Nanoemulsions ; Nanotechnology ; Particle Size ; Pathology/Histopathology ; Pathology/Immunology ; Proteins ; Rats ; Recombinant Proteins - administration & dosage ; Refrigeration ; Toxicology ; Trends ; Tumor necrosis factor-α ; Vaccination ; Vaccines ; Vaccines, DNA - immunology ; Virology/Vaccines ; Viruses ; γ-Interferon</subject><ispartof>PloS one, 2008-08, Vol.3 (8), p.e2954-e2954</ispartof><rights>COPYRIGHT 2008 Public Library of Science</rights><rights>2008 Makidon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Makidon et al. 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c693t-8f00809dd9dc61c86c4704e7bfcc5ebb02bc17b22344c398b252ffdb439a82df3</citedby><cites>FETCH-LOGICAL-c693t-8f00809dd9dc61c86c4704e7bfcc5ebb02bc17b22344c398b252ffdb439a82df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2496893/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2496893/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18698426$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Zimmer, Jacques</contributor><creatorcontrib>Makidon, Paul E</creatorcontrib><creatorcontrib>Bielinska, Anna U</creatorcontrib><creatorcontrib>Nigavekar, Shraddha S</creatorcontrib><creatorcontrib>Janczak, Katarzyna W</creatorcontrib><creatorcontrib>Knowlton, Jessica</creatorcontrib><creatorcontrib>Scott, Alison J</creatorcontrib><creatorcontrib>Mank, Nicholas</creatorcontrib><creatorcontrib>Cao, Zhengyi</creatorcontrib><creatorcontrib>Rathinavelu, Sivaprakash</creatorcontrib><creatorcontrib>Beer, Michael R</creatorcontrib><creatorcontrib>Wilkinson, J Erby</creatorcontrib><creatorcontrib>Blanco, Luz P</creatorcontrib><creatorcontrib>Landers, Jeffrey J</creatorcontrib><creatorcontrib>Baker, Jr, James R</creatorcontrib><title>Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.
Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.
Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy.</description><subject>Adjuvants, Immunologic</subject><subject>Alum</subject><subject>Aluminum</subject><subject>Aluminum sulfate</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibody Formation</subject><subject>Antigens</subject><subject>Aqueous solutions</subject><subject>Bell's palsy</subject><subject>Bells palsy</subject><subject>Biochemistry/Drug Discovery</subject><subject>Biochemistry/Protein Chemistry</subject><subject>Cell-mediated immunity</subject><subject>Chemistry, Pharmaceutical</subject><subject>Chronic infection</subject><subject>Cold storage</subject><subject>Control stability</subject><subject>Cytomegalovirus</subject><subject>Developing countries</subject><subject>Dosage Forms</subject><subject>Electrostatic properties</subject><subject>Emulsions</subject><subject>Enzymes</subject><subject>Evaluation</subject><subject>Global health</subject><subject>Guinea pigs</subject><subject>Health aspects</subject><subject>Hepatitis</subject><subject>Hepatitis B</subject><subject>Hepatitis B surface antigen</subject><subject>Hepatitis B Surface Antigens - administration & dosage</subject><subject>Hepatitis B Surface Antigens - immunology</subject><subject>Hepatitis B vaccines</subject><subject>Hepatitis B Vaccines - administration & dosage</subject><subject>Hepatitis B virus</subject><subject>High temperature</subject><subject>Humans</subject><subject>Hydration</subject><subject>Hydrophobicity</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Immunity</subject><subject>Immunization</subject><subject>Immunoassay</subject><subject>Immunogenicity</subject><subject>Immunoglobulin A</subject><subject>Immunoglobulin 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BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Makidon, Paul E</au><au>Bielinska, Anna U</au><au>Nigavekar, Shraddha S</au><au>Janczak, Katarzyna W</au><au>Knowlton, Jessica</au><au>Scott, Alison J</au><au>Mank, Nicholas</au><au>Cao, Zhengyi</au><au>Rathinavelu, Sivaprakash</au><au>Beer, Michael R</au><au>Wilkinson, J Erby</au><au>Blanco, Luz P</au><au>Landers, Jeffrey J</au><au>Baker, Jr, James R</au><au>Zimmer, Jacques</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2008-08-13</date><risdate>2008</risdate><volume>3</volume><issue>8</issue><spage>e2954</spage><epage>e2954</epage><pages>e2954-e2954</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hepatitis B virus infection remains an important global health concern despite the availability of safe and effective prophylactic vaccines. Limitations to these vaccines include requirement for refrigeration and three immunizations thereby restricting use in the developing world. A new nasal hepatitis B vaccine composed of recombinant hepatitis B surface antigen (HBsAg) in a novel nanoemulsion (NE) adjuvant (HBsAg-NE) could be effective with fewer administrations.
Physical characterization indicated that HBsAg-NE consists of uniform lipid droplets (349+/-17 nm) associated with HBsAg through electrostatic and hydrophobic interactions. Immunogenicity of HBsAg-NE vaccine was evaluated in mice, rats and guinea pigs. Animals immunized intranasally developed robust and sustained systemic IgG, mucosal IgA and strong antigen-specific cellular immune responses. Serum IgG reached > or = 10(6) titers and was comparable to intramuscular vaccination with alum-adjuvanted vaccine (HBsAg-Alu). Normalization showed that HBsAg-NE vaccination correlates with a protective immunity equivalent or greater than 1000 IU/ml. Th1 polarized immune response was indicated by IFN-gamma and TNF-alpha cytokine production and elevated levels of IgG(2) subclass of HBsAg-specific antibodies. The vaccine retains full immunogenicity for a year at 4 degrees C, 6 months at 25 degrees C and 6 weeks at 40 degrees C. Comprehensive pre-clinical toxicology evaluation demonstrated that HBsAg-NE vaccine is safe and well tolerated in multiple animal models.
Our results suggest that needle-free nasal immunization with HBsAg-NE could be a safe and effective hepatitis B vaccine, or provide an alternative booster administration for the parenteral hepatitis B vaccines. This vaccine induces a Th1 associated cellular immunity and also may provide therapeutic benefit to patients with chronic hepatitis B infection who lack cellular immune responses to adequately control viral replication. Long-term stability of this vaccine formulation at elevated temperatures suggests a direct advantage in the field, since potential excursions from cold chain maintenance could be tolerated without a loss in therapeutic efficacy.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>18698426</pmid><doi>10.1371/journal.pone.0002954</doi><tpages>e2954</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2008-08, Vol.3 (8), p.e2954-e2954 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1312295198 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adjuvants, Immunologic Alum Aluminum Aluminum sulfate Animal models Animals Antibodies Antibody Formation Antigens Aqueous solutions Bell's palsy Bells palsy Biochemistry/Drug Discovery Biochemistry/Protein Chemistry Cell-mediated immunity Chemistry, Pharmaceutical Chronic infection Cold storage Control stability Cytomegalovirus Developing countries Dosage Forms Electrostatic properties Emulsions Enzymes Evaluation Global health Guinea pigs Health aspects Hepatitis Hepatitis B Hepatitis B surface antigen Hepatitis B Surface Antigens - administration & dosage Hepatitis B Surface Antigens - immunology Hepatitis B vaccines Hepatitis B Vaccines - administration & dosage Hepatitis B virus High temperature Humans Hydration Hydrophobicity Immune response Immune system Immunity Immunization Immunoassay Immunogenicity Immunoglobulin A Immunoglobulin G Immunoglobulin G - blood Immunoglobulins Immunology/Antigen Processing and Recognition Immunology/Immune Response Immunology/Innate Immunity Infection Infectious Diseases/Epidemiology and Control of Infectious Diseases Infectious Diseases/Viral Infections Influenza Interferon Laboratory animals Lymphocytes B Lymphocytes T Medicine Mice Mucosa Nanoemulsions Nanotechnology Particle Size Pathology/Histopathology Pathology/Immunology Proteins Rats Recombinant Proteins - administration & dosage Refrigeration Toxicology Trends Tumor necrosis factor-α Vaccination Vaccines Vaccines, DNA - immunology Virology/Vaccines Viruses γ-Interferon |
| title | Pre-clinical evaluation of a novel nanoemulsion-based hepatitis B mucosal vaccine |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T16%3A52%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pre-clinical%20evaluation%20of%20a%20novel%20nanoemulsion-based%20hepatitis%20B%20mucosal%20vaccine&rft.jtitle=PloS%20one&rft.au=Makidon,%20Paul%20E&rft.date=2008-08-13&rft.volume=3&rft.issue=8&rft.spage=e2954&rft.epage=e2954&rft.pages=e2954-e2954&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0002954&rft_dat=%3Cgale_plos_%3EA472636128%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1312295198&rft_id=info:pmid/18698426&rft_galeid=A472636128&rft_doaj_id=oai_doaj_org_article_303f5a70839f42438c4dfc98bd0d09b2&rfr_iscdi=true |